Animal models for well defined congenital malformations are obtainable through a controlled use of teratogenic agents. The use of retinoic acid and other conventional teratogens in obtaining localized anomalies in limbs and craniofacial areas is being perfected. Early development of these malformations is studied in tissue culture to locate the initial sites of effect involved in teratogenesis. The behavior of mesenchyme and epithelial cells of the presumptive organs is investigated with particular regard to their interactions, migratory abilities, properties of aggregations, rates of cell division, cell death, and onset and maintenance of biosynthesis of chosen so they may permit an evaluation of the relative importance of each of the above developmental events, or a combination of them, in the orgin of a particular type of malformation. Current organ culture and whole embryo culture procedures are being adapted to provide information for distinguishing between a direct and an indirect effect (through maternal or placental mechanisms) of teratogenic agents. Whole mounts and routine histologic and cytochemical methods are employed for morphologic study. Radioautography, radiochemical procedures, microfractionation, and electrophoretic analyses are used for quantitative studies on the biosynthesis of: general proteins, collagen, glycosaminoglycans, and DNA. Specific alterations in the cytoplasmic organelles of cells responsible for the synthesis of these products are being investigated with the transmission electron microscope. The architecture and composition of the extracellular matrix are studied by means of specific stains and enzymatic digestion in conjunction with electron microscopy. Bibliographic references: Greene, R.M. and D.M. Kochhar: Limb development in mouse embryos. Protection against teratogenic effects of 6-diazo-5-oxonorleucine (DON) in vivo and in vitro. J. Embryol. Exp. Morph. 33: 355-370, 1975. Greene, R.M. and D.M. Kochhar: Some aspects of corticosteroid induced cleft plate: A review. Teratology 11: 47-56, 1975.